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2.
Ann Oncol ; 26(9): 1980-1987, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26037795

ABSTRACT

BACKGROUND: BRAF inhibitors (BRAFi) improve survival in metastatic melanoma patients (MMP) but the duration of clinical benefit is limited by development of drug resistance. Here, we investigated whether the expression of programmed death-ligand 1 (PD-L1) and the density of tumor-infiltrating mononuclear cells (TIMC) predict the occurrence of resistance, hence affecting the clinical outcome in BRAFi-treated MMP. METHODS: PD-L1 expression (cutoff 5%) was analyzed by immunohistochemistry with two different antibodies in BRAF(V600)-mutated formalin-fixed and paraffin-embedded samples from 80 consecutive MMP treated with BRAFi at a single institution. TIMC were evaluated by conventional hematoxylin and eosin staining. RESULTS: Forty-six and 34 patients received vemurafenib and dabrafenib, respectively. Membranous expression of PD-L1 was detected in 28/80 (35%) of patients. At multivariate analysis, absence of tumoral PD-L1 staining [odd ratio (OR) 10.8, 95% confidence interval (CI) 2.7-43.3, P < 0.001] and the presence of TIMC (OR 6.5, 95% CI 1.7-24.3, P < 0.005) were associated with a better response to treatment. Median progression-free survival (PFS) and overall survival were 10 and 15 months, respectively. By multivariate assessment, PD-L1 expression [hazard ratio (HR) 4.3, 95% CI 2.1-8.7, P < 0.0001] and absence of TIMC (HR 2.5, 95% CI 1.4-4.7, P < 0.002) correlated with shorter PFS. PD-L1 overexpression (HR 6.2, 95% CI 2.8-14.2, P < 0.0001) and absence of TIMC (HR 3.1, 95% CI 1.5-6.5, P < 0.002) were independent prognostic factors for melanoma-specific survival. CONCLUSION: Our results provide the first proof-of-principle evidence for the predictive and prognostic relevance of PD-L1 immunohistochemical expression and density of immune cell infiltration in BRAF(V600)-mutated MMP treated with BRAFi.


Subject(s)
B7-H1 Antigen/biosynthesis , Lymphocytes, Tumor-Infiltrating/immunology , Melanoma/drug therapy , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Biomarkers, Tumor/metabolism , Disease-Free Survival , Drug Resistance, Neoplasm/genetics , Female , Humans , Imidazoles/therapeutic use , Indoles/therapeutic use , Lymphocyte Count , Male , Melanoma/genetics , Melanoma/mortality , Middle Aged , Oximes/therapeutic use , Proto-Oncogene Proteins B-raf/genetics , Retrospective Studies , Sulfonamides/therapeutic use , Vemurafenib , Young Adult
3.
Drugs Aging ; 31(4): 283-9, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24604085

ABSTRACT

BACKGROUND: Poor adherence may have a major impact on clinical outcome, contributing to substantial worsening of disease, increased health care costs and even death. With increasing numbers of medications, low adherence is a growing concern, seriously undermining the benefits of current medical care. Little is known about medication adherence among older adults living at home and requiring complex medication regimens. OBJECTIVE: The aim of this study was to describe adherence to drug prescriptions in a cohort of elderly patients receiving polypharmacy, discharged from an internal medicine ward. METHODS: A sample of elderly patients (65 years of age or older) discharged from an internal medicine ward in Italy throughout 2012 were enrolled. They were followed for 3 months after discharge with a structured telephone interview to collect information on drug regimens and medication adherence 15-30 days (first follow-up) and 3 months (second follow-up) after discharge. Demographic variables including age, sex, marital status and caregiver were collected. RESULTS: Among 100 patients recruited, information on medication adherence was available for, respectively, 89 and 79 patients at the first and second follow-ups. Non-adherence was reported for 49 patients (55.1 %) at the first follow-up and for 55 (69.6 %) 3 months from discharge. Voluntary withdrawal of a drug and change of dosage without medical consultation were the main reasons for non-adherence at both follow-ups. The number of drugs prescribed at discharge was related to medication non-adherence at both follow-up interviews. No association was found between age and non-adherence. Only 25 patients (28.1 %) at the first follow-up and 20 (25.3 %) at the second understood the reasons for their medications. CONCLUSIONS: Low medication adherence is a real, complex problem for older patients receiving polypharmacy. We found that the increasing number of drugs prescribed at hospital discharge is correlated to non-adherence and a high percentage of patients did not understand the purpose of their medications. Simplification of drug regimens and reduction of pill burdens as well as better explanations of the reason for the medications should be targets for intervention.


Subject(s)
Medication Adherence/statistics & numerical data , Polypharmacy , Aged , Aged, 80 and over , Humans , Patient Discharge
4.
Eur J Radiol ; 82(11): 1964-72, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23787273

ABSTRACT

Introduction MRI abnormalities in the postictal period might represent the effect of the seizure activity, rather than its structural cause. Material and Methods Retrospective review of clinical and neuroimaging charts of 26 patients diagnosed with seizure-related MR-signal changes. All patients underwent brain-MRI (1.5-Tesla, standard pre- and post-contrast brain imaging, including DWI-ADC in 19/26) within 7 days from a seizure and at least one follow-up MRI, showing partial or complete reversibility of the MR-signal changes. Extensive clinical work-up and follow-up, ranging from 3 months to 5 years, ruled out infection or other possible causes of brain damage. Seizure-induced brain-MRI abnormalities remained a diagnosis of exclusion. Site, characteristics and reversibility of MRI changes, and association with characteristics of seizures were determined. Results MRI showed unilateral (13/26) and bilateral abnormalities, with high (24/26) and low (2/26) T2-signal, leptomeningeal contrast-enhancement (2/26), restricted diffusion (9/19). Location of abnormality was cortical/subcortical, basal ganglia, white matter, corpus callosum, cerebellum. Hippocampus was involved in 10/26 patients. Reversibility of MRI changes was complete in 15, and with residual gliosis or focal atrophy in 11 patients. Reversibility was noted between 15 and 150 days (average, 62 days). Partial simple and complex seizures were associated with hippocampal involvement (p=0.015), status epilepticus with incomplete reversibility of MRI abnormalities (p=0.041). Conclusions Seizure or epileptic status can induce transient, variably reversible MRI brain abnormalities. Partial seizures are frequently associated with hippocampal involvement and status epilepticus with incompletely reversible lesions. These seizure-induced MRI abnormalities pose a broad differential diagnosis; increased awareness may reduce the risk of misdiagnosis and unnecessary intervention.


Subject(s)
Algorithms , Brain/pathology , Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Seizures/pathology , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Reproducibility of Results , Sensitivity and Specificity , Young Adult
5.
Forensic Sci Int ; 229(1-3): e1-5, 2013 Jun 10.
Article in English | MEDLINE | ID: mdl-23582265

ABSTRACT

We report the case of a 70-year-old woman found dead in her apartment in the South of Italy in February 2011. The detailed data showed that the victim was affected by familiar-type paranoid schizophrenia. This finding was confirmed by the discovery of antipsychotic and tricyclic antidepressant drugs in the house and the deposition of her psychiatric therapist. Before the autopsy, a multislice computed tomography (MSCT) scanning of the thoracic and facial maxillo-cervical area was performed that has allowed anatomical identification and diagnosis of a mechanical obstruction as the cause of death. The autopsy has showed the presence of materials obstructing the trachea totally. Histological and toxicological investigations were carried out on the victim. The toxicological investigation has shown the presence of metabolites of tricyclic antidepressants and antipsychotics in the blood and urine. The histology showed the presence of foreign-origin materials (starch fibres) inside the pulmonary alveolus. The cause of death was asphyxia due to obstruction by food-origin material. In this case the radiological data have been compared with the autopsy and toxicological and histological data. The comparison of results has shown that MSCT scanning may aid in identification of occlusion and then in determination of the cause of death. In conclusion, MSCT scanning can be proposed in the cases of suspected asphyxia, as the screening procedure of first instance to produce preliminary information useful to rapidly develop the successive autopsy performance.


Subject(s)
Airway Obstruction/diagnostic imaging , Airway Obstruction/pathology , Asphyxia/etiology , Autopsy/methods , Foreign Bodies/diagnostic imaging , Foreign Bodies/pathology , Aged , Airway Obstruction/etiology , Bread , Esophagus/pathology , Female , Humans , Jaw, Edentulous, Partially/complications , Multidetector Computed Tomography , Periodontal Diseases/complications , Trachea/pathology
6.
Int J Immunopathol Pharmacol ; 26(1): 199-206, 2013.
Article in English | MEDLINE | ID: mdl-23527722

ABSTRACT

Heart failure (HF) is a multifactorial disorder in which clinical, environmental and genetic components take part. For this reason it is possible that common gene variants could affect development, progression and response to pharmacological therapy. In recent years the role of AGEs in the pathogenesis of cardiovascular diseases has become recognized but little is known about the role of the AGE–RAGE system in heart failure. The aim of the present study was to identify possible relationship between -374 T/A RAGE gene polymorphism with heart failure. The population in this study consists of 386 subjects with HF, selected according to the presence of depressed Left Ventricular Ejection Fraction (LVEF) less than45 percent, and 639 patients with CAD documented at coronary angiography. Within the population with HF there are 228 patients with disease secondary to not ischemic cause and 158 with post-ischemic condition. The sample of AA genotype was significantly lower in patients with post-ischemic HF in respect to HF secondary to non-ischemic causes (pless than0.001). A significant difference between the two groups was also observed regarding the allele frequency. In addition, differences in the allelic and the genotypic frequencies of homozygous genotypes were found between the HF patients free from evidence of coronary significant lesions and patients with at least one hemodynamically significant coronary lesion, both HF and CAD. In patients with at least one vessel compromised the presence of A allele and the homozygous AA genotype were significantly lower than in patients with lesion-free coronary. In conclusion, our research reveals that the -374 T/A polymorphism is related to the genesis of atherosclerotic coronary artery disease but not to its evolution. The protective role of AA genotype in respect to atheromatous disease is therefore confirmed also in the HF population with non-ischemic origin.


Subject(s)
Coronary Artery Disease/genetics , Heart Failure/genetics , Receptors, Immunologic/genetics , Aged , Coronary Angiography , Coronary Artery Disease/diagnostic imaging , Female , Heart Failure/diagnostic imaging , Humans , Male , Middle Aged , Polymorphism, Genetic , Receptor for Advanced Glycation End Products
7.
J Neurol ; 259(11): 2452-9, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22648476

ABSTRACT

Stereotypies are simple or complex involuntary/unvoluntary behaviors, common in fronto-temporal dementia (FTD), but not studied in other types of degenerative dementias. The aim was to investigate stereotypy frequency and type in patients with FTD, Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and Parkinson's disease with dementia (PDD) in a multicenter observational study; and to investigate the relation of stereotypies to cognitive, behavioral and motor impairment. One hundred fifty-five consecutive outpatients (45 AD, 40 FTD, 35 PSP and 35 PDD) were studied in four hospitals in northern Italy. Stereotypies were examined by the five-domain Stereotypy Rating Inventory. Cognition was examined by the Mini Mental State and Frontal Assessment Battery, neuropsychiatric symptoms by the Neuropsychiatric Inventory, and motor impairment and invalidity by the Unified Parkinson's Disease Rating Scale part III, and activities of daily living. Stereotypies were present in all groups. FTD and PDD had the greatest frequency of one-domain stereotypies; FTD also had the greatest frequency of two-or-more domain stereotypies; movement stereotypies were the most common stereotypies in all groups. AD patients had fewer stereotypies than the other groups. Stereotypies are not exclusive to FTD, but are also fairly common in PSP and PDD, though less so in AD. Stereotypies may be underpinned by dysfunctional striato-frontal circuits, known to be damaged in PSP and PDD, as well as FTD.


Subject(s)
Alzheimer Disease/epidemiology , Frontotemporal Dementia/epidemiology , Parkinson Disease/epidemiology , Stereotypic Movement Disorder/epidemiology , Supranuclear Palsy, Progressive/epidemiology , Aged , Aged, 80 and over , Alzheimer Disease/diagnosis , Alzheimer Disease/psychology , Dementia/diagnosis , Dementia/epidemiology , Dementia/psychology , Female , Frontotemporal Dementia/diagnosis , Frontotemporal Dementia/psychology , Humans , Male , Middle Aged , Neuropsychological Tests , Parkinson Disease/diagnosis , Parkinson Disease/psychology , Stereotypic Movement Disorder/diagnosis , Stereotypic Movement Disorder/psychology , Supranuclear Palsy, Progressive/diagnosis , Supranuclear Palsy, Progressive/psychology
8.
Neuropathol Appl Neurobiol ; 38(4): 367-78, 2012 Jun.
Article in English | MEDLINE | ID: mdl-21851375

ABSTRACT

AIMS: Recent studies propose the neurotrophin receptor p75NTR as a marker for muscle satellite cells and a key regulator of regenerative processes after injury. Here, we investigated the contribution of cellular compartments other than satellite cells and regenerating myofibres to p75NTR signal in diseased skeletal muscle. METHODS: We checked regulation of p75NTR expression in muscle biopsies from patients with inflammatory myopathies (polymyositis, dermatomyositis and inclusion body myositis), or Becker muscular dystrophy, and in nonmyopathic tissues. Quantitative PCR, immunohistochemistry, immunofluorescence or electron microscopy were used. RNA interference approaches were applied to myotubes to explore p75NTR function. RESULTS: We found p75NTR transcript and protein upregulation in all inflammatory myopathies but not in dystrophic muscle, suggesting a role for inflammatory mediators in induction of p75NTR expression. In inflamed muscle p75NTR was localized on distinct cell types, including immune cells and mature myofibres. In vitro assays on human myotubes confirmed that inflammatory factors such as IL-1 could induce p75NTR. Finally, RNA interference experiments in differentiated cells showed that, in the absence of p75NTR, myotubes were more susceptible to apoptosis when exposed to inflammatory stimuli. CONCLUSIONS: Our observations that p75NTR is upregulated on skeletal myofibres in inflammatory myopathies in vivo and promotes resistance to inflammatory mediators in vitro suggest that neurotrophin signalling through p75NTR may mediate a tissue-protective response to inflammation in skeletal myofibres.


Subject(s)
Inflammation/metabolism , Muscle Fibers, Skeletal/metabolism , Myofibrils/metabolism , Myositis/metabolism , Nerve Growth Factors/metabolism , Nerve Tissue Proteins/biosynthesis , Receptors, Nerve Growth Factor/biosynthesis , Adolescent , Adult , Aged , Cell Survival , Child , Female , Humans , Immunohistochemistry , Inflammation/pathology , Male , Microscopy, Electron, Transmission , Middle Aged , Muscle Fibers, Skeletal/pathology , Myofibrils/pathology , Myositis/pathology , Signal Transduction/physiology , Young Adult
9.
Radiol Med ; 116(1): 1-14, 2011 Feb.
Article in English, Italian | MEDLINE | ID: mdl-20981503

ABSTRACT

UNLABELLED: This paper analyses off-label prescribing of the iodinated organic and magnetic resonance (MR) contrast media used in diagnostic imaging and evaluates the liability profiles and medicolegal issues associated with such use. The term off-label generally indicates the use of known drugs for which new scientific evidence suggests use in a manner and in clinical scenarios not explicitly addressed by the drug data sheet and is outside the indications for which the medication was approved. In addition, the term also indicates the use of drugs with a different route of administration and dosage from those indicated in the information leaflet. Intravascular contrast media used in diagnostic imaging are drugs in the complete sense of the term, even though they have unique characteristics which in many ways distinguish them from other pharmacological agents. The off-label use of contrast media in diagnostic imaging is a little-investigated field and most commonly, but not exclusively, applies to gadolinium-based contrast media used in MR angiography as well as cardiac and paediatric applications. In particular, the off-label use of contrast media mostly concerns deviations from the recommended dose. As contrast media are to all effects pharmaceutical agents, their off-label use can be considered admissible within the limitations laid down by the Italian law in force (Article 3 of Law 94/98) and its interpretation, i.e. the following criteria must be present: the lack of a valid diagnostic alternative; written informed consent by the patient; the presence of scientific publications validated at the international level; assumption of responsibility by the radiologist. CONCLUSIONS: The use of contrast media in modern image-guided medicine is essential. In cases in which the information contained in the information leaflet is modified and updated in any way whatsoever (indications, dosage, at others), specifically if restrictions are introduced in accordance with the law in force, the pharmaceutical industry must provide formal and timely notification to radiologists. On their part as prescribers and users of contrast media, radiologists must remain up to date regarding any changes in indications, dosage and route of administration. Lastly, we propose that the radiology report includes not only the type but also the dose of contrast medium used.


Subject(s)
Contrast Media/pharmacology , Magnetic Resonance Imaging , Off-Label Use , Contrast Media/administration & dosage , Contrast Media/adverse effects , Humans , Iodine , Italy , Off-Label Use/economics , Off-Label Use/ethics , Off-Label Use/legislation & jurisprudence
10.
Int J Immunopathol Pharmacol ; 24(4): 905-13, 2011.
Article in English | MEDLINE | ID: mdl-22230397

ABSTRACT

Inflammation plays a key role in atherosclerosis. Galectin-3 is a macrophage- and endothelium-derived mediator actively involved in the regulation of many aspects of inflammatory cell behaviour. The aim of this study is to quantify plasma Galectin-3 in patients with coronary artery disease (CAD) and different clinical manifestation at the moment of observation in order to verify whether Galectin-3 could be a useful biomarker of atherosclerotic state. We enrolled 125 patients affected by CAD, angiographically documented (70 stable, 55 unstable). They underwent accurate examinations and anamnestic data was collected. The most important traditional risk factors, such as age, hypertension, and body mass index, were reported. Plasma Galectin-3 was quantified using an ELISA kit. Unstable patients (n = 55) had a higher plasma Galectin-3 levels in respect to the stable subjects (27.75 ng/mL (19.27-39.09) vs 6.48 ng/ml (4.88-8.83), p<0.001. A trend in correlation between plasma Galectin-3 levels and number of vessels compromised seems to be present: CAD patients with three-vessel disease had higher levels of Galectin-3 than patients with one-or two-vessel disease (17.39 ng/ml (10.75-29.82) vs 9.18 ng/ml (5.56-23.22), p= 0.058. The significantly higher plasma Galectin-3 levels in patients with unstable angina in respect to the stable angina confirm the involvement of Galectin-3 in promoting macrophage activation and monocyte attraction. Despite the distribution of CAD in patients with acute and chronic coronary disease being similar, we may hypothesize that Galectin-3 could be a useful biomarker of atherosclerotic plaque and in particular of its destabilization.


Subject(s)
Acute Coronary Syndrome/blood , Angina, Unstable/blood , Galectin 3/blood , Myocardial Infarction/blood , Acute Coronary Syndrome/diagnostic imaging , Acute Coronary Syndrome/immunology , Aged , Angina, Unstable/diagnostic imaging , Angina, Unstable/immunology , Biomarkers/blood , Chi-Square Distribution , Coronary Angiography , Disease Progression , Enzyme-Linked Immunosorbent Assay , Female , Humans , Italy , Male , Middle Aged , Myocardial Infarction/diagnostic imaging , Myocardial Infarction/immunology , Predictive Value of Tests , Risk Assessment , Risk Factors , Severity of Illness Index , Up-Regulation
11.
Int J Immunopathol Pharmacol ; 23(3): 917-25, 2010.
Article in English | MEDLINE | ID: mdl-20943064

ABSTRACT

Low levels of the regulatory peptide apelin have been reported in patients with lone atrial fibrillation (AF). We evaluate the potential utility of assessing apelin plasma levels as a predictor of AF recurrence in individuals presenting for electrical cardioversion. Plasma levels of apelin, brain natriuretic peptide (BNP) and high-sensitivity C-reactive protein were measured in 93 patients, with persistent AF before successful external electrical cardioversion. Significantly lower apelin plasma levels were found in patients with AF recurrence as respect to population with persistence of sinus rhythm during a six months follow-up. The hazard increased with duration of AF, left atrial dimension, BNP concentrations. Subjects with apelin levels below the median had a hazard ratio of 3.1 of arrhythmia recurrence with respect to those with high apelin levels (p<0.05). A significant difference in BNP levels was found between patients with and without AF recurrence during the follow-up. After adjusting for potential confounders, both BNP and apelin retained their statistical significance as independent predictors of arrhythmia recurrence. Patients with both low apelin and elevated BNP had a worse prognosis compared with those with either low apelin or elevated BNP alone. Low plasma apelin levels before external electrical cardioversion are an independent prognostic factor for arrhythmia recurrence in patients with AF treated with antiarrhythmic drugs. Apelin may be of particular value for the identification of high-risk patients in addition to BNP.


Subject(s)
Arrhythmias, Cardiac/blood , Atrial Fibrillation/blood , Intercellular Signaling Peptides and Proteins/blood , Aged , Analysis of Variance , Anti-Arrhythmia Agents/therapeutic use , Apelin , Arrhythmia, Sinus/physiopathology , Arrhythmias, Cardiac/drug therapy , Arrhythmias, Cardiac/etiology , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Biomarkers/blood , Brain-Derived Neurotrophic Factor/blood , C-Reactive Protein/metabolism , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Predictive Value of Tests , Recurrence , Risk Factors
12.
Nanoscale ; 2(10): 2230-6, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20835434

ABSTRACT

Multitasking nanoparticles are gaining great attention for smart drug delivery systems. The exploration of the nano-scale opens new concrete opportunities for revealing new properties and undiscovered cell-particle interactions. Here we present a biodegradable nanoporous silicon nanoparticle that can be successfully employed for in vivo targeted drug delivery and sustained release. The bare nanoporous nanocarriers can be accurately designed and fabricated with an effective control of porosity, surface chemistry and particle size, up to a few nm. The proposed nanoparticles exhibit several remarkable features including high payload, biodegradability, no toxicity, and multiple loading in water without the need of additional chemical reagents at room temperature. The targeting strategy is based on phage display technology that was successfully used to discover cell surface binding peptide for murine B lymphoma A20 cell line. The peptide used in combination with the nanoporous nanoparticles allows an efficient in vivo targeting, a sustained release and a sensible therapeutic effect.


Subject(s)
B-Lymphocytes/metabolism , Drug Carriers/chemistry , Drug Delivery Systems , Nanotechnology/methods , Neoplasms/drug therapy , Water/chemistry , Animals , Antineoplastic Agents/administration & dosage , B-Lymphocytes/drug effects , Biocompatible Materials/chemistry , Cell Line, Tumor , Drug Screening Assays, Antitumor/methods , Female , Hydrophobic and Hydrophilic Interactions , Mice , Mice, Inbred BALB C , Nanostructures/chemistry , Solubility
13.
Mult Scler ; 15(8): 899-906, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19667018

ABSTRACT

BACKGROUND: Epidemiological studies on the association between allergic disorders, T-helper type 2 (Th2) mediated, and multiple sclerosis (MS), a T-helper type 1 (Th1)/Th17-mediated disease, provided conflicting results. OBJECTIVE: The aim of this study was to further examine the association between allergic disorders and MS. METHODS: The association between MS and previous medical history of any type of allergy has been investigated in a population-based case-control study conducted in Northern Italy, based on telephone interviews to 423 cases and 643 population controls (refusal rates 3.7% and 9.4%, respectively). Controls were a random sample of the general population. RESULTS: A history of atopic allergies seems to confer protection against MS (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.38-0.89; P = 0.012). In particular, the prevalence of allergic asthma was 4.9% in people with MS and 12% in control subjects (OR = 0.38; 95% CI 0.22-0.66, P < 0.01). No association was found between MS and nonatopic allergies. CONCLUSIONS: Our findings are confirmatory of the putative protective effect of Th2-mediated disorders on Th1 immune responses associated with MS. A unifying theory on the mechanisms by which previous history of atopic allergies may modify the risk of MS is still lacking.


Subject(s)
Hypersensitivity/epidemiology , Multiple Sclerosis/epidemiology , Adolescent , Adult , Case-Control Studies , Female , Humans , Hypersensitivity/immunology , Italy/epidemiology , Logistic Models , Male , Middle Aged , Multiple Sclerosis/immunology , Multiple Sclerosis/prevention & control , Odds Ratio , Population Surveillance , Prevalence , Registries , Risk Assessment , Risk Factors , Th1 Cells/immunology , Th2 Cells/immunology , Young Adult
14.
Clin Nephrol ; 72(1): 79-80, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19640392

ABSTRACT

Renal alterations in hypothyroidism include decreased glomerular filtration rate and renal plasma flow. We herein report a case of amiodarone -induced hypothyroidism associated with a rapid decrease of renal function, reversible upon amiodarone withdrawal. A 72-year-old man presented to our clinic in August 2007 reporting a recent deterioration of renal function. Ten weeks before he was admitted to another hospital for a supraventricular tachyarrhythmia treated with carvedilol 12.5 mg/day and amiodarone 400 mg/day. On admission, laboratory tests revealed altered renal function (serum creatinine 6 mg/dl, blood urea nitrogen 78 mg/dl) and severe hypothyroidism (free T4 0.27 pg/ml, free T3 1.49 pg/ml, TSH 183.36 mU/l). Amiodarone and carvedilol were stopped, while levothyroxine 75 mcg/die was started. After three months renal function had completely recovered to 1.9 mg/dl, BUN 28 mg/dl, with concurrent improvement of thyroid function free T4 14.2 pg/ml, free T3 6.4 pg/ml, TSH 15.5 mU/l.


Subject(s)
Acute Kidney Injury/etiology , Amiodarone/adverse effects , Anti-Arrhythmia Agents/adverse effects , Hypothyroidism/chemically induced , Hypothyroidism/complications , Aged , Humans , Kidney Function Tests , Male , Tachycardia, Supraventricular/drug therapy
16.
J Neurol Neurosurg Psychiatry ; 80(7): 790-3, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19237383

ABSTRACT

OBJECTIVE: To examine the association between the presence of arrhythmia in type 1 myotonic dystrophy (DM1) and clinical-genetic variables, evaluating their role as predictors of the risk of arrhythmia. METHODS: 245 patients with genetically proven DM1 underwent clinical and non-invasive cardiological evaluation. Severity of muscular involvement was assessed according to the 5 point Muscular Disability Rating Score (MDRS). Data were analysed by univariate and multivariate models. RESULTS: 245 patients were examined and cardiac arrhythmias were found in 63 subjects, 40 of whom required a device implant. Statistical analyses revealed that men had more than double the risk of developing arrhythmias compared with women (p = 0.018). Addition of each year of age caused an increased risk of arrhythmia equal to 3% (p = 0.030). Subjects with MDRS 5 had a risk of arrhythmia 12 times higher than patients with MDRS 1-2 (p<0.001). Although all of these variables were significantly associated with cardiac rhythm dysfunction, they had a low sensitivity for the prediction of arrhythmic risk CONCLUSION: Male sex, age and muscular disability were strongly associated with the development of arrhythmia in DM1. However, all of these variables were weak predictors of arrhythmic risk. These results suggest that other factors may be involved in the development of cardiac conduction abnormalities in DM1.


Subject(s)
Arrhythmias, Cardiac/epidemiology , Arrhythmias, Cardiac/physiopathology , Myotonic Dystrophy/epidemiology , Myotonic Dystrophy/physiopathology , Adult , Age Factors , Aged , Analysis of Variance , Arrhythmias, Cardiac/diagnosis , Arrhythmias, Cardiac/genetics , Cohort Studies , Electrocardiography , Female , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Myotonic Dystrophy/diagnosis , Myotonic Dystrophy/genetics , Risk Assessment , Risk Factors , Severity of Illness Index , Sex Factors , Young Adult
17.
Radiol Med ; 113(8): 1157-70, 2008 Dec.
Article in English, Italian | MEDLINE | ID: mdl-18958408

ABSTRACT

PURPOSE: The aim of the study was to assess the reliability of whole-body magnetic resonance imaging (WB-MRI) in detecting skeletal metastasis and to compare the results with those of bone scintigraphy (BS). MATERIALS AND METHODS: Thirty-three patients (21 women, 12 men, median age 58 years, range 27-78) were enrolled. Histological proof of malignancy was obtained in all cases. The primary tumour was unknown in 1 patient. BS and WB-MRI were performed as staging procedures in 15 patients, during the follow-up in 6 and to investigate pain in 9 and neurological symptoms in 3. Bone metastases were recorded for 8 different skeletal segments (ribs, skull, cervicothoracic spine, lumbosacral spine, clavicle-scapula-sternum, pelvis, upper extremities and lower extremities) in all patients, for a total of 264 examined areas. RESULTS: Bone metastases were detected in 18 patients (55%). In 15/33 patients, WB-MRI and BS were concordantly negative. BS revealed focal metastatic uptake in 72%, whereas WB-MRI was positive in 89%. Results differed in seven patients. WB-MRI was positive but BS was negative in five cases. Two patients with negative WB-MRI had focal and intense uptake in the ribs on BS. Out of 264 examined areas, bone metastases were detected in 34 (13%). WB-MRI revealed tumour spread in 26/34 areas (76%) and BS in 21/34 areas only (62%). CONCLUSIONS: WB-MRI is a reliable method for screening patients with suspected skeletal metastases, although BS still remains a useful tool. WB-MRI is also advantageous because it reveals extraskeletal and soft tissue metastases.


Subject(s)
Bone Neoplasms/diagnosis , Bone Neoplasms/secondary , Magnetic Resonance Imaging , Adult , Aged , Bone Neoplasms/diagnostic imaging , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Radionuclide Imaging , Reproducibility of Results
18.
Poult Sci ; 87(6): 1012-21, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18492987

ABSTRACT

Two experiments were conducted to assess the effect of genotype, production system, and nutrition on performance and livability of meat chickens for niche markets. Slow-growing (SG) and fast-growing genotypes (FG) were raised for 91 and 63 d, respectively, in experiment 1 (females) or 84 and 56 d, respectively, in experiment 2 (males). In each trial, SG were placed before FG to achieve a similar BW at processing. In experiment 1, each genotype was assigned to 8 pens of 20 birds each, with 4 pens within each genotype raised indoors in a conventional research facility or in a small facility with outdoor access. All birds were fed a low-nutrient diet. In experiment 2, genotype assignment to pens was as in experiment 1; however, 4 pens within each genotype were fed a low-nutrient diet or a conventional diet, and birds were raised indoors. Birds were gait-scored and commercially processed; legs were examined for tibial dyschon-droplasia lesions and scanned for bone mineral density. In experiment 1, FG gained more weight than SG (P < 0.05) even though they were placed later. Outdoor access increased feed intake, and feed efficiency was poorer (P< 0.05). Fast-growing genotypes had higher breast meat yield, whereas SG had higher wing and leg yields (P < 0.05). In experiment 2, the low-nutrient diet reduced (P< 0.05) gain of the SG; FG increased feed intake of the low-nutrient diet such that their gain was unaffected (P> 0.05). For FG, the low-nutrient diet resulted in a poorer (P < 0.05) feed efficiency. Although weight gain of the FG was maintained on the low-nutrient diet, breast yield was reduced (P < 0.05). Genotype affected bone health in both experiments, with SG having better gait scores and less tibial dyschondroplasia (P < 0.05). Outdoor access and the low-nutrient diet also resulted in better gait score (P < 0.05). These data indicate differences among genotypes and provide information about the efficiency and potential for alternative poultry systems.


Subject(s)
Animal Feed , Chickens/growth & development , Chickens/genetics , Housing, Animal , Animals , Chickens/anatomy & histology , Chickens/physiology , Genotype , Growth/genetics , Longevity , Nutritive Value , Weight Gain
19.
Acta Anaesthesiol Scand ; 51(10): 1327-30, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17944635

ABSTRACT

BACKGROUND: Ultrasound guidance for central venous cannulation is advised by recent guidelines, but is not being applied in everyday practice. The purpose of this study was to determine the reduction in complications when applying an ultrasound locating device for internal jugular vein catheterization. METHODS: An observational study was conducted from November 2004 to October 2005 in a tertiary neurosurgical hospital on 300 patients undergoing internal jugular vein cannulation using an ultrasound technique. Patients were not randomized and operators were trained using theoretical and practical courses. Prior to the study, the investigators, who were consultant anaesthesiologists, had to perform at least 20 successful supervised cannulations. RESULTS: Cannulation was successful in all cases. The incidence of arterial puncture was 2.7%, and multiple venous punctures represented the main minor complication (14%). Bivariate analysis of the overall complications revealed no significant correlation with age group, American Society of Anesthesiologists' (ASA) classification, body mass index, or position and diameter of the vein. CONCLUSIONS: Ultrasound cannulation of the internal jugular vein minimized complications. These could be avoided when new ultrasound probes and specific needles are introduced.


Subject(s)
Catheterization/adverse effects , Jugular Veins/diagnostic imaging , Female , Humans , Male , Treatment Outcome , Ultrasonography
20.
Br J Anaesth ; 99(6): 906-11, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17962241

ABSTRACT

BACKGROUND: The predictive value of the El-Ganzouri risk index (EGRI) for difficult intubation has been evaluated using Macintosh laryngoscopy as reference standard. The Glidescope videolaryngoscope provides improved visualization of the glottis. We studied the predictive value of the EGRI using videolaryngoscopy as reference standard. METHODS: Data from two subsequent groups of patients, intubated with Macintosh laryngoscopy (ML, n = 994) and videolaryngoscopy (VL, n = 843), were retrospectively analysed. The EGRI was taken as index test. The two types of laryngoscopy were adopted as reference for the presence of Cormack and Lehane grading III-IV. For both groups, sensitivity, specificity, and positive and negative post-test probabilities (PTP) were calculated for thresholds on the EGRI scale. Receiver operating characteristic curves and corresponding areas (AUC) were obtained. RESULTS: Sensitivity and specificity were 69.7% and 66.3% at the cut-off value of 2 in the ML group, and 93.3% and 76.6% at the cut-off value of 3 in the VL group. Corresponding positive and negative PTP were 12.81% and 3.15% in the ML group, and 6.73% and 0.16% in the VL group. At the threshold of 4, positive and negative PTP were 31.34% and 4.85% in the ML group. At the threshold of 7, positive and negative PTP were 85.71% and 1.08% in the VL group. The AUC was 0.74 in the ML group and 0.91 in the VL group. CONCLUSIONS: The predictive value of the EGRI may have been underestimated due to limited accuracy of Macintosh laryngoscopy. Using videolaryngoscopy, the EGRI might be reconsidered as a decisional tool.


Subject(s)
Intubation, Intratracheal/methods , Laryngoscopy/methods , Adolescent , Adult , Aged , Aged, 80 and over , Equipment Design , Female , Humans , Intubation, Intratracheal/adverse effects , Intubation, Intratracheal/instrumentation , Laryngoscopes , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , Risk Assessment/methods , Video Recording
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